Project Summary/Abstract Moraxella catarrhalis is acknowledged as an important cause of otitis media in infants and very young children and can also cause exacerbations of chronic obstructive pulmonary disease in adults. Little is known about the gene products that allow M. catarrhalis to colonize the nasopharyngeal mucosa and then cause disease in the respiratory tract. The ability of this organism to colonize the mucosal surface of the nasopharynx is crucial to its ability to cause disease in other anatomic regions because this colonization event provides a foothold for M. catarrhalis in its human host. It has been shown that M. catarrhalis forms a biofilm in vivo. We have now identified two different surface proteins (UspA1 and Hag) that form projections on the surface of this bacterium and which are involved in biofilm development. In the first Specific Aim, we will perform structure-function analysis to identify the specific regions of the UspA1 and Hag proteins that are essential for biofilm development. In the second Specific Aim, we will identify those M. catarrhalis surface proteins that are induced or up-regulated when this organism attaches to human cells or when this organism grows in vivo. In the third Specific Aim, we will use mutant analysis together with a chinchilla model of nasopharyngeal colonization by M. catarrhalis to determine which of these surface-exposed proteins of this organism are essential for nasopharyngeal colonization. Finally, in the fourth Specific Aim, we will use this chinchilla model to determine which of these surface proteins can induce the synthesis of antibodies which inhibit or prevent nasopharyngeal colonization by M. catarrhalis. Information gained from this study will directly benefit efforts to develop an effective vaccine to prevent respiratory tract disease caused by M. catarrhalis